Longitudinal dynamics of immune responses after mRNA and inactivated COVID-19 vaccination, boosters, and breakthrough infections in Malaysia

Aug 28, 2025Vaccine

Changes in immune responses over time after mRNA and inactivated COVID-19 vaccines, boosters, and infections in Malaysia

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Abstract

BNT162b2 vaccine elicited a stronger anti-spike antibody response of 3.0 log U/mL compared to CoronaVac at 3 months post-second dose.

Anti-nucleocapsid antibody seroconversion was 50.3% in CoronaVac recipients, indicating limited immune response against the N protein.
Booster vaccinations with mRNA-based regimens enhanced anti-spike antibody responses to 3.6-3.7 log U/mL for up to 6 months.
Homologous CoronaVac boosters resulted in lower antibody levels of 2.8 log U/mL.
Breakthrough infections caused a rapid increase in anti-nucleocapsid antibody levels, which declined back to pre-infection levels within 3 months.
In healthy individuals, T cell responses increased two years post-booster, while they declined in kidney transplant recipients despite strong antibody responses.

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During the COVID-19 pandemic, Malaysia adopted heterologous vaccine booster strategies using BNT162b2 (Pfizer), CoronaVac (Sinovac) and ChAdOx1 nCoV-19 (AstraZeneca) due to vaccine shortages. However, longitudinal data on immune durability and breakthrough infections, especially in immunocompromised groups, remain limited. This study evaluates humoral response in healthy individuals after primary vaccine series and booster dose, and assesses long-term hybrid immunity up to two years post-booster in both healthy individuals and immunocompromised kidney transplant recipients (KTRs). BNT162b2 vaccine elicited a stronger anti-spike (anti-S) antibody response (3.0 log U/mL) compared to CoronaVac (1.6 log U/mL) at 3 months post-second dose. Anti-nucleocapsid (anti-N) antibody seroconversion was 50.3 % in CoronaVac recipients, suggesting limited humoral responses against N protein. Booster vaccination with homologous or heterologous mRNA-based regimens (BNT162b2/BNT162b2, ChAdOx1 nCoV-19/BNT162b2, and CoronaVac/BNT162b2) further enhanced anti-S antibody responses (3.6-3.7 log U/mL) for up to 6 months, whereas homologous CoronaVac/CoronaVac boosters yielded lower antibody levels (2.8 log U/mL). Breakthrough infections triggered a rapid rise in anti-N antibody, followed by a decline back to pre-infection levels within 3 months. In individuals infected two years after booster vaccination, T cell responses increased in healthy participants but declined in KTRs despite strong antibody responses, suggesting immunosuppressive therapy may impair T cell activation. These findings highlight the need for comprehensive immune assessments to guide preventive strategies, especially for immunocompromised populations.

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Longitudinal dynamics of immune responses after mRNA and inactivated COVID-19 vaccination, boosters, and breakthrough infections in Malaysia

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